mTOR Mediated Anti-Cancer Drug Discovery.

Drug Discovery Today. Therapeutic Strategies
Qingsong LiuNathanael S Gray

Abstract

The mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase and the founding member of a signaling pathway that regulates many fundamental features of cell growth and division. In cells, mTOR acts as the catalytic subunit of two functionally distinct complexes, called mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2). Together, these complexes coordinate a variety of processes that include protein translation, autophagy, proliferation, survival and metabolism in response to nutrient, energy and growth factor signals. Consistent with its role as a growth-promoting pathway, numerous studies have found that Mtor signaling is hyper-activated in a broad spectrum of human cancers. In particular, mTORC2 is considered a primary effector of the phosphatidylinositol-3-kinase (PI3K) signaling pathway, which is mutated in a majority of human cancers, in part through its ability to phosphorylate and regulate the proto-oncogene Akt/PKB. Many biological functions of mTOR have been pharmacologically explored using the natural product rapamycin, an allosteric inhibitor that has been reviewed extensively elsewhere. This review will focus specifically on the development of small molecule ATP-competitive inhib...Continue Reading

References

Oct 10, 2001·Therapeutic Drug Monitoring·K L Napoli, P J Taylor
Nov 11, 2003·Trends in Biochemical Sciences·Brendan D Manning, Lewis C Cantley
Mar 16, 2004·Science·Yardena SamuelsVictor E Velculescu
May 4, 2004·Nature Reviews. Cancer·Mary-Ann Bjornsti, Peter J Houghton
Oct 27, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wallace H MondesireFunda Meric-Bernstam
Apr 28, 2005·Current Biology : CB·Xiaomeng LongJoseph Avruch
Oct 18, 2005·Current Opinion in Cell Biology·Dos D SarbassovDavid M Sabatini
Apr 11, 2006·Molecular Cell·Dos D SarbassovDavid M Sabatini
May 16, 2006·Cancer Cell·Qi-Wen FanWilliam A Weiss
Nov 3, 2006·Nature Reviews. Drug Discovery·Thomas RückleChristian Rommel
Mar 6, 2007·Nature Chemical Biology·Jimmy A BlairKevan M Shokat
Mar 21, 2007·Genes & Development·Ville Hietakangas, Stephen M Cohen
Jul 7, 2007·Cancer Cell·David A Guertin, David M Sabatini
Aug 31, 2007·Clinical Pharmacology and Therapeutics·C M Hartford, M J Ratain
Nov 13, 2007·Biochimica Et Biophysica Acta·Romina MaroneMatthias P Wymann
Feb 6, 2008·Bioorganic & Medicinal Chemistry Letters·Frédéric StaufferCarlos García-Echeverría
May 24, 2008·Science·Yasemin SancakDavid M Sabatini
Oct 14, 2008·Nature Chemical Biology·Beth ApselZachary A Knight
Oct 18, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Mandar R BhondeNilesh M Dagia
Jan 20, 2009·The Journal of Biological Chemistry·Carson C ThoreenNathanael S Gray
Feb 13, 2009·PLoS Biology·Morris E FeldmanKevan M Shokat
Feb 13, 2009·Molecular Biology of the Cell·Nao HosokawaNoboru Mizushima
Feb 20, 2009·Molecular Biology of the Cell·Chang Hwa JungDo-Hyung Kim
Feb 20, 2009·Organic & Biomolecular Chemistry·Teather J SundstromDennis L Wright
Mar 5, 2009·The Journal of Biological Chemistry·Ian G GanleyXuejun Jiang
Apr 1, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Funda Meric-Bernstam, Ana Maria Gonzalez-Angulo
Apr 3, 2009·Nature Reviews. Molecular Cell Biology·Xiaoju Max Ma, John Blenis
Apr 23, 2009·Science Signaling·David A Guertin, David M Sabatini
May 1, 2009·The Biochemical Journal·Juan M García-MartínezDario R Alessi
Aug 1, 2009·Nature Reviews. Drug Discovery·Pixu LiuJean J Zhao
Sep 8, 2009·Bioorganic & Medicinal Chemistry Letters·Keith A MenearKurt G Pike
Nov 11, 2009·Cell Cycle·Boris ShorKer Yu

❮ Previous
Next ❯

Citations

Apr 30, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Arshawn Sami, Michael Karsy
Mar 30, 2012·Expert Reviews in Molecular Medicine·Tabetha Sundin, Patricia Hentosh
Dec 19, 2013·Journal of Medicinal Chemistry·Thibault SauratSylvain Routier
Apr 26, 2011·Head & Neck Oncology·Yu-Min LiaoYun Yen
Mar 24, 2011·Future Medicinal Chemistry·Abhijit RoychowdhurySanjay Kumar
Jan 1, 2012·ISRN Otolaryngology·Wei GaoThian-Sze Wong
Aug 5, 2014·Archives of Gynecology and Obstetrics·HaiXia LiKeng Shen
May 9, 2012·Cellular and Molecular Life Sciences : CMLS·Jeonghyun AhnHeuiran Lee
Feb 2, 2012·Chemical Society Reviews·Kyung-Hwa BaekInjae Shin
Aug 27, 2013·Expert Review of Clinical Pharmacology·Monica M MitaSant P Chawla
Oct 21, 2011·Expert Opinion on Investigational Drugs·Bruno VincenziGiuseppe Tonini
Feb 18, 2016·Journal of Pharmaceutical Sciences·Ankit K RochaniD Sakthi Kumar
Dec 14, 2011·Biochemical Pharmacology·M Espona-FiedlerR Pérez-Tomás
Feb 22, 2011·Drug Discovery Today·Yan-Jie ZhangX F Steven Zheng
Jun 2, 2012·PPAR Research·Joseph VamecqStéphane Rocchi
Sep 8, 2011·International Journal of Cancer. Journal International Du Cancer·Salah-Eddin Al-BatranAtsushi Ohtsu
Feb 24, 2015·European Journal of Medicinal Chemistry·Ashish Radadiya, Anamik Shah
Sep 19, 2015·Biochemical and Biophysical Research Communications·Ling WuEnkun Han
Nov 20, 2014·Chemistry, an Asian Journal·Konstantin V KudryavtsevJih-Hwa Guh
Dec 16, 2011·The Biochemical Journal·Brian MagnusonDiane C Fingar
Apr 26, 2015·European Journal of Medicinal Chemistry·Xiao-Meng WangSan-Qi Zhang
Jul 19, 2013·Biochemical Society Transactions·Karl KatholnigThomas Weichhart
Sep 21, 2011·Progress in Neurobiology·Maria Jimenez-SanchezDavid C Rubinsztein
Jul 15, 2015·Bioorganic & Medicinal Chemistry·Vunnam VenkateswarluSanghapal D Sawant
Mar 5, 2015·Biochimica Et Biophysica Acta·Antonio GentilellaGeorge Thomas
Apr 12, 2015·Journal of Biochemistry·Chitose Oneyama, Masato Okada
Nov 29, 2011·Journal of Hepatology·Beicheng Sun, Michael Karin
Jan 21, 2012·Cancer Letters·Yekaterina Y ZaytsevaB Mark Evers
Sep 18, 2012·The American Journal of Pathology·Farhatullah SyedArdeshir Bayat
Feb 6, 2015·The Journal of Clinical Investigation·Helin Vakifahmetoglu-NorbergJunying Yuan
Apr 24, 2015·PloS One·Kyoko KakumotoChitose Oneyama

❮ Previous
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